Literature DB >> 19275170

Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models.

Felix M Rivas1, James P Stables, Lauren Murphree, Rahul V Edwankar, Chitra R Edwankar, Shengming Huang, Hiteshkumar D Jain, Hao Zhou, Samarpan Majumder, Subramanian Sankar, Bryan L Roth, Joachim Ramerstorfer, Roman Furtmüller, Werner Sieghart, James M Cook.   

Abstract

The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, ip) were observed for compounds 2-4 in the subcutaneous metrazole seizure (scMET) test. In rats, orally (po) the TI was >5 to 105. These compounds represent novel leads in the search for anticonvulsants devoid of sedative, ataxic, and amnestic side effects.

Entities:  

Mesh：

Substances：

Year:  2009        PMID： 19275170      PMCID： PMC2671240          DOI： 10.1021/jm801652d

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  19 in total

1.  Pyrazolopyridinones as functionally selective GABAA ligands.

Authors:  Wesley P Blackaby; John R Atack; Frances Bromidge; Richard Lewis; Michael G N Russell; Alison Smith; Keith Wafford; Ruth M McKernan; Leslie J Street; José L Castro
Journal:  Bioorg Med Chem Lett       Date:  2005-11-15       Impact factor: 2.823

2.  TPA023 [7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a nonsedating anxiolytic in rodents and primates.

Authors:  John R Atack; Keith A Wafford; Spencer J Tye; Susan M Cook; Bindi Sohal; Andrew Pike; Cyrille Sur; David Melillo; Linda Bristow; Fran Bromidge; Ian Ragan; Julie Kerby; Les Street; Robert Carling; José L Castro; Paul Whiting; Gerard R Dawson; Ruth M McKernan
Journal:  J Pharmacol Exp Ther       Date:  2005-09-23       Impact factor: 4.030

3.  Diazepam metabolism in normal man. II. Serum concentration and clinical effect after oral administration and cumulation.

Authors:  L Hillestad; T Hansen; H Melsom
Journal:  Clin Pharmacol Ther       Date:  1974-09       Impact factor: 6.875

Review 4.  GABA(A)-receptor subtypes: clinical efficacy and selectivity of benzodiazepine site ligands.

Authors:  E R Korpi; M J Mattila; W Wisden; H Lüddens
Journal:  Ann Med       Date:  1997-08       Impact factor: 4.709

5.  Contribution of GABAA receptor subtypes to the anxiolytic-like, motor, and discriminative stimulus effects of benzodiazepines: studies with the functionally selective ligand SL651498 [6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyridol[3,4-b]indol-1-one].

Authors:  Stephanie C Licata; Donna M Platt; James M Cook; P V V Srirama Sarma; Guy Griebel; James K Rowlett
Journal:  J Pharmacol Exp Ther       Date:  2005-02-01       Impact factor: 4.030

6.  Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit.

Authors:  Michael G N Russell; Robert W Carling; John R Atack; Frances A Bromidge; Susan M Cook; Peter Hunt; Catherine Isted; Matt Lucas; Ruth M McKernan; Andrew Mitchinson; Kevin W Moore; Robert Narquizian; Alison J Macaulay; David Thomas; Sally-Anne Thompson; Keith A Wafford; José L Castro
Journal:  J Med Chem       Date:  2005-03-10       Impact factor: 7.446

7.  Requirement of alpha5-GABAA receptors for the development of tolerance to the sedative action of diazepam in mice.

Authors:  Carolien van Rijnsoever; Marcus Täuber; Mohamed Khaled Choulli; Ruth Keist; Uwe Rudolph; Hanns Mohler; Jean Marc Fritschy; Florence Crestani
Journal:  J Neurosci       Date:  2004-07-28       Impact factor: 6.167

8.  Changes in human drug metabolism after long-term exposure to hypnotics.

Authors:  I H Stevenson; M Browning; J Crooks; K O'Malley
Journal:  Br Med J       Date:  1972-11-11

9.  Anticonflict and rotarod impairing effects of alprazolam and diazepam in rat after acute and subchronic administration.

Authors:  B Söderpalm; E Eriksson; J A Engel
Journal:  Prog Neuropsychopharmacol Biol Psychiatry       Date:  1989       Impact factor: 5.067

10.  Tricyclic pyridones as functionally selective human GABAA alpha 2/3 receptor-ion channel ligands.

Authors:  James Crawforth; John R Atack; Susan M Cook; Karl R Gibson; Alan Nadin; Andrew P Owens; Andrew Pike; Michael Rowley; Alison J Smith; Bindi Sohal; Francine Sternfeld; Keith Wafford; Leslie J Street
Journal:  Bioorg Med Chem Lett       Date:  2004-04-05       Impact factor: 2.823
View more
  18 in total

Review 1.  A novel GABA(A) receptor pharmacology: drugs interacting with the α(+) β(-) interface.

Authors:  Werner Sieghart; Joachim Ramerstorfer; Isabella Sarto-Jackson; Zdravko Varagic; Margot Ernst
Journal:  Br J Pharmacol       Date:  2012-05       Impact factor: 8.739

2.  Anxiolytic-like effects of 8-acetylene imidazobenzodiazepines in a rhesus monkey conflict procedure.

Authors:  Bradford D Fischer; Stephanie C Licata; Rahul V Edwankar; Zhi-Jian Wang; Shengming Huang; Xiaohui He; Jianming Yu; Hao Zhou; Edward M Johnson; James M Cook; Roman Furtmüller; Joachim Ramerstorfer; Werner Sieghart; Bryan L Roth; Samarpan Majumder; James K Rowlett
Journal:  Neuropharmacology       Date:  2010-08-18       Impact factor: 5.250

3.  Comparison of cell expression formats for the characterization of GABA(A) channels using a microfluidic patch clamp system.

Authors:  Qin Chen; Peter D Yim; Nina Yuan; Juliette Johnson; James M Cook; Steve Smith; Cristian Ionescu-Zanetti; Zhi-Jian Wang; Leggy A Arnold; Charles W Emala
Journal:  Assay Drug Dev Technol       Date:  2012-05-10       Impact factor: 1.738

4.  Further evaluation of the potential anxiolytic activity of imidazo[1,5-a][1,4]diazepin agents selective for α2/3-containing GABAA receptors.

Authors:  J M Witkin; R Cerne; M Wakulchik; J S; S D Gleason; T M Jones; G Li; L A Arnold; J-X Li; J M Schkeryantz; K R Methuku; J M Cook; M M Poe
Journal:  Pharmacol Biochem Behav       Date:  2017-04-22       Impact factor: 3.533

5.  The Positive Allosteric Modulator of α2/3-Containing GABAA Receptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury.

Authors:  Jeffrey M Witkin; Guanguan Li; Lalit K Golani; Wenhui Xiong; Jodi L Smith; Xingjie Ping; Farjana Rashid; Rajwana Jahan; Rok Cerne; James M Cook; Xiaoming Jin
Journal:  J Pharmacol Exp Ther       Date:  2019-11-06       Impact factor: 4.030

6.  Enhancing the function of alpha5-subunit-containing GABAA receptors promotes action potential firing of neocortical neurons during up-states.

Authors:  Berthold Drexler; Stefan Zinser; Shengming Huang; Michael M Poe; Uwe Rudolph; James M Cook; Bernd Antkowiak
Journal:  Eur J Pharmacol       Date:  2013-02-01       Impact factor: 4.432

7.  Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys.

Authors:  Angela N Duke; Zhiqiang Meng; Donna M Platt; John R Atack; Gerard R Dawson; David S Reynolds; V V N Phani Babu Tiruveedhula; Guanguan Li; Michael Rajesh Stephen; Werner Sieghart; James M Cook; James K Rowlett
Journal:  J Pharmacol Exp Ther       Date:  2018-05-02       Impact factor: 4.030

8.  Novel positive allosteric modulators of GABAA receptors: do subtle differences in activity at alpha1 plus alpha5 versus alpha2 plus alpha3 subunits account for dissimilarities in behavioral effects in rats?

Authors:  Miroslav M Savić; Samarpan Majumder; Shengming Huang; Rahul V Edwankar; Roman Furtmüller; Srdan Joksimović; Terry Clayton; Joachim Ramerstorfer; Marija M Milinković; Bryan L Roth; Werner Sieghart; James M Cook
Journal:  Prog Neuropsychopharmacol Biol Psychiatry       Date:  2010-01-13       Impact factor: 5.067

9.  Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone.

Authors:  George Gallos; Elizabeth Townsend; Peter Yim; Laszlo Virag; Yi Zhang; Dingbang Xu; Matthew Bacchetta; Charles W Emala
Journal:  Am J Physiol Lung Cell Mol Physiol       Date:  2012-11-30       Impact factor: 5.464

10.  Insights into functional pharmacology of α₁ GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?

Authors:  Srđan Joksimović; Zdravko Varagic; Jovana Kovačević; Michael Van Linn; Marija Milić; Sundari Rallapalli; Tamara Timić; Werner Sieghart; James M Cook; Miroslav M Savić
Journal:  Psychopharmacology (Berl)       Date:  2013-05-18       Impact factor: 4.530
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.